Automatic Radiotherapy Planning for Glioblastoma Radiotherapy With Sparing of the Hippocampus and nTMS-Defined Motor Cortex

BackgroundNavigated transcranial magnetic stimulation (nTMS) of the motor cortex has been successfully implemented into radiotherapy planning by a number of studies. Furthermore, the hippocampus has been identified as a radiation-sensitive structure meriting particular sparing in radiotherapy. This study assesses the joint protection of these two eloquent brain regions for the treatment of glioblastoma (GBM), with particular emphasis on the use of automatic planning.Patients and MethodsPatients with motor-eloquent brain glioblastoma who underwent surgical resection after nTMS mapping of the motor cortex and adjuvant radiotherapy were retrospectively evaluated. The radiotherapy treatment plans were retrieved, and the nTMS-defined motor cortex and hippocampus contours were added. Four additional treatment plans were created for each patient: two manual plans aimed to reduce the dose to the motor cortex and hippocampus by manual inverse planning. The second pair of re-optimized plans was created by the Auto-Planning algorithm. The optimized plans were compared with the “Original” plan regarding plan quality, planning target volume (PTV) coverage, and sparing of organs at risk (OAR).ResultsA total of 50 plans were analyzed. All plans were clinically acceptable with no differences in the PTV coverage and plan quality metrics. The OARs were preserved in all plans; however, overall the sparing was significantly improved by Auto-Planning. Motor cortex protection was feasible and significant, amounting to a reduction in the mean dose by >6 Gy. The dose to the motor cortex outside the PTV was reduced by >12 Gy (mean dose) and >5 Gy (maximum dose). The hippocampi were significantly improved (reduction in mean dose: ipsilateral >6 Gy, contralateral >4.6 Gy; reduction in maximum dose: ipsilateral >5 Gy, contralateral >5 Gy). While the dose reduction using Auto-Planning was generally better than by manual optimization, the radiated total monitor units were significantly increased.ConclusionConsiderable dose sparing of the nTMS-motor cortex and hippocampus could be achieved with no disadvantages in plan quality. Auto-Planning could further contribute to better protection of OAR. Whether the improved dosimetric protection of functional areas can translate into improved quality of life and motor or cognitive performance of the patients can only be decided by future studies.

FLASH Radiotherapy Using Single-Energy Proton PBS Transmission Beams for Hypofractionation Liver Cancer: Dose and Dose Rate Quantification

PurposeThis work aims to study the dose and ultra-high-dose rate characteristics of transmission proton pencil beam scanning (PBS) FLASH radiotherapy (RT) for hypofractionation liver cancer based on the parameters of a commercially available proton system operating under FLASH mode.Methods and MaterialsAn in-house treatment planning software (TPS) was developed to perform intensity-modulated proton therapy (IMPT) FLASH-RT planning. Single-energy transmission proton PBS plans of 4.5 Gy × 15 fractions were optimized for seven consecutive hepatocellular carcinoma patients, using 2 and 5 fields combined with 1) the minimum MU/spot chosen between 100 and 400, and minimum spot time (MST) of 2 ms, and 2) the minimum MU/spot of 100, and MST of 0.5 ms, based upon considerations in target uniformities, OAR dose constraints, and OAR FLASH dose rate coverage. Then, the 3D average dose rate distribution was calculated. The dose metrics for the mean dose of Liver-GTV and other major OARs were characterized to evaluate the dose quality for the different combinations of field numbers and minimum spot times compared to that of conventional IMPT plans. Dose rate quality was evaluated using 40 Gy/s volume coverage (V40Gy/s).ResultsAll plans achieved favorable and comparable target uniformities, and target uniformity improved as the number of fields increased. For OARs, no significant dose differences were observed between plans of different field numbers and the same MST. For plans using shorter MST and the same field numbers, better sparing was generally observed in most OARs and was statistically significant for the chest wall. However, the FLASH dose rate coverage V40Gy/s was increased by 20% for 2-field plans compared to 5-field plans in most OARs with 2-ms MST, which was less evident in the 0.5-ms cases. For 2-field plans, dose metrics and V40Gy/s of select OARs have large variations due to the beam angle selection and variable distances to the targets. The transmission plans generally yielded inferior dosimetric quality to the conventional IMPT plans.ConclusionThis is the first attempt to assess liver FLASH treatment planning and demonstrates that it is challenging for hypofractionation with smaller fractional doses (4.5 Gy/fraction). Using fewer fields can allow higher minimum MU/spot, resulting in higher OAR FLASH dose rate coverages while achieving similar plan quality compared to plans with more fields. Shorter MST can result in better plan quality and comparable or even better FLASH dose rate coverage.

Minimum-monitor-unit optimization via a stochastic coordinate descent method

Objective: Deliverable proton spots are subject to the minimum monitor-unit (MMU) constraint. The MMU optimization problem with relatively large MMU threshold remains mathematically challenging due to its strong nonconvexity. However, the MMU optimization is fundamental to proton radiotherapy (RT), including efficient IMPT, proton arc delivery (ARC), and FLASH-RT. This work aims to develop a new optimization algorithm that is effective in solving the MMU problem. Approach: Our new algorithm is primarily based on stochastic coordinate decent (SCD) method. It involves three major steps: first to decouple the determination of active sets for dose-volume-histogram (DVH) planning constraints from the MMU problem via iterative convex relaxation method; second to handle the nonconvexity of the MMU constraint via SCD to localize the index set of nonzero spots; third to solve convex subproblems projected to this convex set of nonzero spots via projected gradient descent method. Main results: Our new method SCD is validated and compared with alternating direction method of multipliers (ADMM) for IMPT and ARC. The results suggest SCD had better plan quality than ADMM, e.g., the improvement of conformal index (CI) from 0.51 to 0.71 during IMPT, and from 0.22 to 0.86 during ARC for the lung case. Moreover, SCD successfully handled the nonconvexity from large MMU threshold that ADMM failed to handle, in the sense that (1) the plan quality from ARC was worse than IMPT (e.g., CI was 0.51 with IMPT and 0.22 with ARC for the lung case), when ADMM was used; (2) in contrast, with SCD, ARC achieved better plan quality than IMPT (e.g., CI was 0.71 with IMPT and 0.86 with ARC for the lung case), which is compatible with more optimization degrees of freedom from ARC compared to IMPT. Significance: To the best of our knowledge, our new MMU optimization method via SCD can effectively handle the nonconvexity from large MMU threshold that none of the current methods can solve. Therefore, we have developed a unique MMU optimization algorithm via SCD that can be used for efficient IMPT, proton arc delivery (ARC), FLASH-RT, and other particle RT applications where large MMU threshold is desirable (e.g., for the delivery of high dose rates or/and a large number of spots).

Verification of an optimizer algorithm by the beam delivery evaluation of intensity-modulated arc therapy plans

Background In the case of dynamic radiotherapy plans, the fractionation schemes can have dosimetric effects. Our goal was to define the effect of the fraction dose on the plan quality and the beam delivery. Materials and methods Treatment plans were created for 5 early-stage lung cancer patients with different dose schedules. The planned total dose was 60 Gy, fraction dose was 2 Gy, 3 Gy, 5 Gy, 12 Gy and 20 Gy. Additionally renormalized plans were created by changing the prescribed fraction dose after optimization. The dosimetric parameters and the beam delivery parameters were collected to define the plan quality and the complexity of the treatment plans. The accuracy of dose delivery was verified with dose measurements using electronic portal imaging device (EPID). Results The plan quality was independent from the used fractionation scheme. The fraction dose could be changed safely after the optimization, the delivery accuracy of the treatment plans with changed prescribed dose was not lower. According to EPID based measurements, the high fraction dose and dose rate caused the saturation of the detector, which lowered the gamma passing rate. The aperture complexity score, the gantry speed and the dose rate changes were not predicting factors for the gamma passing rate values. Conclusions The plan quality and the delivery accuracy are independent from the fraction dose, moreover the fraction dose can be changed safely after the dose optimization. The saturation effect of the EPID has to be considered when the action limits of the quality assurance system are defined.

An adaptive spot placement method on Cartesian grid for pencil beam scanning proton therapy

Pencil beam scanning (PBS) proton radiotherapy (RT) offers flexible proton spot placement near treatment targets for delivering tumoricidal radiation dose to tumor targets while sparing organs-at-risk (OAR). Currently the spot placement is mostly based on a non-adaptive sampling (NS) strategy on a Cartesian grid. However, the spot density or spacing during NS is a constant for the Cartesian grid that is independent of the geometry of tumor targets, and thus can be suboptimal in terms of plan quality (e.g., target dose conformality) and delivery efficiency (e.g., number of spots). This work develops an adaptive sampling (AS) spot placement method on the Cartesian grid that fully accounts for the geometry of tumor targets. Compared with NS, AS places (1) a relatively fine grid of spots at the boundary of tumor targets to account for the geometry of tumor targets and treatment uncertainties (setup and range uncertainty) for improving dose conformality, and (2) a relatively coarse grid of spots in the interior of tumor targets to reduce the number of spots for improving delivery efficiency and robustness to the minimum-minitor-unit (MMU) constraint. The results demonstrate that (1) AS achieved comparable plan quality with NS for regular MMU and substantially improved plan quality from NS for large MMU, using merely about 10% of spots from NS, where AS was derived from the same Cartesian grid as NS; (2) on the other hand, with similar number of spots, AS had better plan quality than NS consistently for regular and large MMU.